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ZusammenfassungIn diesem österreichweiten Consensus Statement sind die Empfehlungen zum Umgang mit latenter Tuberkulose bei Therapie mit biologischen und „targeted synthetic“ DMARDs zusammengefasst. Die wesentlichen Fragen bezüglich des Screenings und präventiver Therapie wurden von Expertinnen und Experten aus den Fachbereichen Rheumatologie, Pneumologie, Infektiologie, Dermatologie und Gastroenterologie auf Basis der vorhandenen Daten diskutiert und dann in einer Abstimmung zum gemeinsamen Konsens gebracht. Dabei wurde auch differenziert auf die unterschiedlichen Therapien eingegangen, und klare Empfehlungen wurden formuliert.

SummaryThis publication provides a thorough analysis of the most relevant topics concerning the management of latent tuberculosis when using biologic and targeted synthetic Disease Modifying Antirheumatic Drugs (DMARDs) by a multidisciplinary, select committee of Austrian physicians. The committee includes members of the Austrian Societies for Rheumatology and Rehabilitation, Pulmonology, Infectiology, Dermatology and Gastroenterology. Consensus was reached on issues regarding screening and treatment of latent tuberculosis and includes separate recommendations for each biologic and targeted synthetic DMARD.

ObjectivesWhile >50% of medical students and residents are women, their proportion drastically diminishes within higher ranks and leadership roles; this is known as the ‘leaky pipeline’. We aimed to evaluate the leaky pipeline among rheumatologists across Europe and to assess determinants inducing rheumatologists to leave hospitals.MethodsExperts in the field of economics developed a questionnaire with scientific focus on the leaky pipeline among rheumatologists, which was distributed electronically by national scientific societies of EULAR countries and by individual contacts. We performed common factor analysis, univariate t-tests and multivariate regression analyses to appraise our dataset.ResultsA total of 311 hospital-based rheumatologists from 23/45 EULAR countries (52.7% females, 47.3% males) answered the questionnaire. The presence of the leaky pipeline was evident for the entire sample. Of 64% female rheumatologists only 34.2% of departments’ directors were female, with noteworthy regional differences. Female doctors reported higher intentions to leave their hospital (β = 0.28, P ConclusionFemale rheumatologists perceive worse job opportunities and satisfaction than males. Many reasons for the leaky pipeline are beyond the control of organizations. Based on our results, organizations should be encouraged to reconsider and adjust their performance management practices to enable an equitable work environment.

OBJECTIVES Predictive data for the development of aortic dilatation (AD) in giant-cell arteritis (GCA) are controversial. The aim was to investigate by computed tomography (CT) the prevalence of AD in a consecutive cohort of GCA patients and controls, and to identify possible predictors for AD. METHODS GCA patients and controls were identified by electronic search and underwent aortic contrast enhanced CT defining AD by aortic diameter adjusted to age, gender and body surface area. Pulse-wave velocity, intima-media thickness (IMT) and laboratory studies including lymphocyte subsets were conducted identifying potential factors associated with AD. Clinical and laboratory parameters at disease onset, occurrence of aortic rupture/dissection before and up to five years after study visit were retrieved by chart review. RESULTS 144 GCA patients and 115 controls were included. GCA patients developed more frequently AD of the ascending and thoracic descending aorta compared to controls (OR 2.60, p = 0.016; OR 3.65, p = 0.005, respectively). Factors associated with AD development of thoracic descending aorta, but not of the ascending aorta, were higher percentages of circulating CD3+CD4+ cells, higher CD4/CD8 ratio, presence of polymyalgia rheumatica and increased carotid IMT at disease onset (OR range 1.10-3.11, all with p

Objectives To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. Methods A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. Results The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. Conclusion The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

This nationwide Austrian consensus statement summarizes the recommendations on the management of latent tuberculosis by treatment with biologic and targeted synthetic DMARDs. The essential questions with respect to screening and preventive treatment were discussed by experts from the disciplines of rheumatology, pneumology, infectious diseases, dermatology and gastroenterology, based on the available data, and then a joint consensus was formed by agreement. This involved a differentiated discussion on the various forms of treatment, and clear recommendations were formulated.In diesem österreichweiten Consensus Statement sind die Empfehlungen zum Umgang mit latenter Tuberkulose bei Therapie mit biologischen und „targeted synthetic“ DMARDs zusammengefasst. Die wesentlichen Fragen bezüglich des Screenings und präventiver Therapie wurden von Expertinnen und Experten aus den Fachbereichen Rheumatologie, Pneumologie, Infektiologie, Dermatologie und Gastroenterologie auf Basis der vorhandenen Daten diskutiert und dann in einer Abstimmung zum gemeinsamen Konsens gebracht. Dabei wurde auch differenziert auf die unterschiedlichen Therapien eingegangen, und klare Empfehlungen wurden formuliert.

Monoclonal gammopathy of undetermined significance (MGUS), a premalignant condition, is associated with various chronic inflammatory rheumatic diseases (RDs) and is frequently observed as an incidental finding during routine work-up. The association of MGUS and chronic RDs is well established, but the impact of RDs on the risk of transformation into overt multiple myeloma (MM) has not been evaluated so far. MGUS patients diagnosed between January 2000 and August 2016 were identified and screened for concomitant RDs. RDs were grouped into antibody (Ab)-mediated RDs and non-Ab–mediated RDs (polymyalgia rheumatica, large-vessel giant cell arteritis, spondyloarthritis, and gout). Progression to MM was defined as a categorical (yes/no) or continuous time-dependent (time to progression) variable. Of 2935 MGUS patients, 255 (9%) had a concomitant RD. MGUS patients diagnosed with non-Ab–mediated RDs had a doubled risk of progression compared with those without a concomitant RD (hazard ratio, 2.1; 95% CI, 1.1-3.9; P = .02). These data translate into a 5-year risk of progression of 4% in MGUS patients without rheumatologic comorbidity, 10% in those with concomitant non-Ab–mediated RDS, and 2% in those with Ab-mediated RDs. By using the complex risk stratification model that includes myeloma protein (M-protein) concentration, immunoglobulin type, and level of free light chain ratio as variables, patients with non-Ab–mediated RDs (n = 57) had the highest risk for progression (hazard ratio, 6.8; 95% CI, 1.5-30.7; P = .01) compared with patients with Ab-mediated RDs (n = 77). Chronic inflammatory diseases have an impact on the risk of MGUS progressing into overt MM, with a doubled risk of transformation observed in patients with non-Ab–mediated RDs. Future research can elucidate whether comorbidities such as RDs should be included in currently applied prognostic MGUS scores.

PMR is an inflammatory rheumatic disease of elderly people characterized by pain and stiffness in the neck, shoulder and pelvic girdles. No specific diagnostic confirmatory tests exist and clinical symptoms, as well as increased acute phase reactants, are unspecific. The diagnostic value of imaging including ultrasound, MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with/without CT for PMR is increasingly studied. These techniques, particularly FDG-PET/CT, may help to detect underlying GCA in PMR patients with an incomplete response to glucocorticoids and/or recurrent relapses. Recent imaging studies provide novel insights into the anatomical basis of inflammation in PMR, particularly at hip and spine, which may help to distinguish this disease from other mimicking conditions. In this review, we discuss novel insights into the pathoanatomy of PMR, compare the diagnostic values of different imaging techniques and summarize current data on the role of imaging for monitoring and outcome prediction.

ObjectivesTo develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.MethodsThe OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.ResultsAgreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff0.37–0.48).ConclusionWe developed a provisional OGUS for potential use in clinical trials.

ObjectivesTo develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).MethodsA systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously.ResultsFive overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment.ConclusionThese are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

Antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) are characterised by a heterogeneous clinical phenotype.1 We report a cluster of 15 patients diagnosed with AAV either de novo (n=11) or with relapsing disease (n=4) during COVID-19 pandemic between February and August 2020. During this period, we observed two major phenomena: (1) an incidence-shift with a ‘COVID-gap’ of no diagnosed AAV cases during the lockdown period (March and April), followed by a ‘postlockdown cluster’ of 14 active patients (8 myeloperoxidase-ANCA, 6 proteinase 3-ANCA vasculitis) in the subsequent 4 months and (2) an increased incidence rate (figure 1 and online supplemental figure S3). Mean creatinine at baseline was 3.66 mg/dL. Inflammatory markers were significantly elevated in most patients, with a mean C reactive protein value of 9.93 mg/dL and an erythrocyte sedimentation rate of 83 mm per first hour. Despite detrimental effects on humoral immunity,2 most patients received two doses of rituximab and methylprednisolone. No severe treatment complications occurred. SARS-CoV-2 PCR and serology were negative in tested patients. Further clinical and radiological characteristics are provided in online supplemental tables S1 and S2).### Supplementary data [annrheumdis-2020-219212supp001.pdf] ### Supplementary data [annrheumdis-2020-219212supp002.pdf] ### Supplementary data [annrheumdis-2020-219212supp003.pdf] ### Supplementary data [annrheumdis-2020-219212supp004.pdf] Figure 1 Timeline of incident ANCA-associates vasculitis cases in 2018, 2019 and 2020. Incident cases are posed on a timeline …

Objective To evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Methods Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. LDA was assessed using the Disease Activity index for Psoriatic Arthritis (DAPSA ⩽ 14), the Psoriatic ArthritiS Disease Activity Score (PASDAS ⩽ 3.2), the Composite Psoriatic Disease Activity Index ⩽ 4, the DAS28-CRP ⩽ 2.8 and the minimal disease activity criteria. Ultrasound was performed at 68 joints and 14 entheses. Minimal ultrasound disease activity (MUDA-j/e) was defined as a Power Doppler score ⩽ 1, respectively at joints, paratendinous tissue, tendons and entheses. A global ultrasound score was calculated by summing Grey Scale and Power Doppler information (GUIS-j/e). Results LDA was present in 33.7–65.0% at baseline and in 44.3–80.6% at follow-up, depending on the criteria used. MUDA-j/e was observed in 16.9% at baseline and in 30% at follow-up. GUIS-j/e was significantly higher in patients with moderate/high disease activity vs LDA according to DAPSA and PASDAS at baseline and DAPSA, PASDAS, Composite Psoriatic Disease Activity Index and minimal disease activity at follow-up. Patients in moderate/high disease activity had MUDA-j/e in 8.1–21.4% at baseline and in 8.3–20.0% at follow-up, depending on the applied clinical composite. MUDA-j/e patients with moderate/high disease activity had higher levels of pain and pain-related items than those with LDA. Conclusion The LDA cut-offs of DAPSA, PASDAS, Composite Psoriatic Disease Activity Index, minimal disease activity, but not DAS28-CRP are capable of distinguishing between high and low ultrasound activity. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity.

ObjectivesTo develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs).MethodsEuropean Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously.ResultsA total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel.ConclusionThese are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs.

Objective To evaluate tender joints (TJ) and swollen joints (SJ) for the assessment of ultrasound (US) defined inflammation in PsA. Methods Eighty-three PsA patients underwent clinical and US examinations at two scheduled study visits 12 months apart. Tenderness and swelling were assessed at 68 and 66 joints, respectively, and US examinations were conducted at all 68 joints. At patient level, associations with clinical composites and US scores were performed using correlations and by analysing patients with predominantly tender (pTender) or swollen joints (pSwollen). At joint level, a Power Doppler (PD) value ≥ 1 was defined as active synovitis. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months. Results SJC showed better correlations with GS/PD scores (r = 0.37/0.47) than with TJC (PD: r = 0.33), while TJC correlated better with patient reported outcomes (PROMs) like patient global assessment (TJC: r = 0.57; SJC r = 0.39). Patients with pTender showed poorer results for PROMs and disease activity scores than patients with pSwollen, but not for laboratory or US markers of inflammation. Swollen joints showed active synovitis in 35% of cases, while only 16% of tender joints were active according to US. Swelling at baseline better predicted active synovitis at the same joint after 12 months [odds ratio (OR) 6.33, P Conclusions SJ are more closely linked with US signs of inflammation as compared with TJ in PsA. Joint swelling is a better predictor for signs of US inflammation than tenderness after one year of follow-up.

Objective.To test the reliability of Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus-based ultrasound definitions for normal and vasculitic temporal and axillary arteries in patients with giant cell arteritis (GCA) and in controls.Methods.A preliminary 1-day meeting and a full 3-day meeting fulfilling OMERACT Ultrasound Group guidelines were held. Temporal and axillary arteries were examined at 2 timepoints by 12 sonographers on 4 patients with GCA and 2 controls. The aim was to test inter- and intrareader reliability for normal findings, halo sign, and compression sign. In both meetings, patients had established GCA. Pathology was more recent in the full meeting, which was preceded by 6 h of training. Scanning time was 15–20 min instead of 10–13 min.Results.In the preliminary exercise, interreader reliabilities were fair to moderate for the overall diagnosis of GCA (Light κ 0.29–0.51), and poor to fair for identifying vasculitis in the respective anatomical segments (Light κ 0.02–0.46). Intrareader reliabilities were moderate (Cohen κ 0.32–0.64). In the main exercise, interreader reliability was good to excellent (Light κ 0.76–0.86) for the overall diagnosis of GCA, and moderate to good (Light κ 0.46–0.71) for identifying vasculitis in the respective anatomical segments. Intrareader reliability was excellent for diagnosis of GCA (Cohen κ 0.91) and good (Cohen κ 0.71–0.80) for the anatomical segments.Conclusion.OMERACT-derived definitions of halo and compression signs of temporal and axillary arteries are reliable in recent-onset GCA if experienced sonographers (> 300 examinations) have 15–20 min for a standardized examination with prior training and apply > 15 MHz probes.

Introduction Sarcoidosis is a systemic granulomatous disease with a variable clinical presentation and disease course. There is still no reliable biomarker available, which assists in the diagnosis or prediction of the clinical course. According to a murine model, the expression level of the metabolic checkpoint kinase mechanistic target of Rapamycin complex 1 (mTORC1) in granulomas of sarcoidosis patients may be used as a clinical biomarker. Material and methods This is a retrospective analysis of 58 patients with histologically confirmed sarcoidosis. Immunohistochemical staining of granulomas from tissue samples was evaluated for the expression of activated mTORC1 signaling, including phosphorylated mTOR, its downstream effectors S6K1, 4EBP1 and the proliferation marker Ki-67. Patients were categorized according to different clinical phenotypes, serum biomarkers, and immunomodulatory therapy. Results All patients showed activated mTORC1 signaling in granulomas, which correlated with its downstream effectors S6K1 and 4EBP1 but was not related to Ki-67 expression. The mTORC1 activity revealed an association neither to disease severity nor the necessity of treatment; however, p-mTOR inversely correlated with cumulative corticosteroid dosage. Conclusion Our data confirm activation of the mTORC1 pathway in sarcoidosis, supporting the hypothesis that mTOR is a significant driver in granuloma formation. However, we could not find a relationship between the degree of mTOR activation and disease severity or the need for therapy.

Objectives The aim of this prospective study was to examine whether ultrasound or clinical abnormalities at enthesal sites predict radiographic progression at entheses in psoriatic arthritis (PsA). Methods Consecutive PsA patients were included and subjected to clinical and ultrasound assessments at 14 entheses at baseline, 6 and 12 months. Radiographs were performed at 0 and 12 months. By US, we investigated structural (erosions, osteophytes) and inflammatory changes [grey scale (0–32) and power Doppler (0–14, range global ultrasound score 0–140)], and radiographs were evaluated for enthesophytes and erosions (score range 0–56). Multivariate regression models were conducted to identify the possible association of clinical and ultrasound findings with radiographic progression. Results We examined 83 patients at baseline, of whom 43 (51.8%) had complete clinical, ultrasound and X-ray data. Twenty-four of 43 patients (55.8%) developed radiographic progression of entheses. These patients were younger (49.6 vs 59.3, P =0.005), had shorter disease duration (9.7 vs 17.9 years, P=0.015) and lower clinical disease activity at 6-months [disease activity in psoriatic arthritis (DAPSA) 6.7 vs 17.0, P=0.018] as compared with patients without progression. Non-progressors had higher ultrasound enthesophyte scores at baseline than progressors (20 vs 15, P Conclusion Our data indicate that radiographic progression at entheses is linked with age, disease duration and ultrasound verified enthesophytes at baseline. No other ultrasound parameter predicted radiographic progression at entheses.

Moiseev et al 1 underlined the main message of the new European League Against Rheumatism (EULAR) recommendations for the use of imaging in large vessel vasculitis (LVV), namely the importance of imaging as a first-line test for the diagnosis of LVV.2 The EULAR task force also emphasised that the recommendations should not be understood as a recommendation against performing temporal artery biopsy (TAB) in giant cell arteritis (GCA), rather a biopsy still has its place when there is diagnostic doubt after having performed imaging or when imaging is not available or not performed with sufficient expertise. When a diagnosis can be …

Background:Tender and Swollen Joint Counts (TJC, SJC) are items of disease activity scores in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Recent studies suggest that TJC do not adequately reflect ongoing inflammation in RA when using Ultrasound (US) as a reference standard, and that pain might be due to other, non-inflammatory causes.1, 2In PsA, the role of tenderness and swelling of joints for reflecting active inflammation has not been well studied so far.Objectives:To evaluate tender (TJ) and swollen joints (SJ) for the assessment of inflammation in PsA.Methods:We performed a prospective study on 83 PsA patients undergoing clinical and ultrasound examinations at two study visits scheduled 12 months apart. Tenderness and swelling were assessed for 68 and 66 joints respectively and US examinations, including grey scale (GS) and power doppler (PD) were conducted at all 68 joints. GS- (range 0-204) und PD sum scores (0-204) were calculated. At patient level, correlations were performed between TJC, SJC and clinical or US values. At joint level a GS value≥1 and/or PD value≥1 was defined as active synovitis, which was compared to whether a joint was tender, swollen or both. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months, taking into consideration the joint site.Results:At baseline the median TJC and SJC for 83 patients was 4 (range 0-59) and 1 (0-20), respectively and the median GSS- and PD sum score was 16 (3-56) and 3 (0-31) respectively. SJC correlated with the GSS sum score (r= 0.37, p=0.004) and PD sum score (r =0.47, pConclusion:SJC are more closely linked with US signs of inflammation as compared to TJC in PsA. While swelling of a joint predicts US inflammation after a year, the information whether the joint is additionally tender or not, gives no additional predictive information.References:[1]Hammer HB, Michelsen B, Sexton J, et al. Swollen, but not tender joints, are independently associated with ultrasound synovitis: results from a longitudinal observational study of patients with established rheumatoid arthritis.Ann Rheum Dis2019;78:1179-85.[2]Hammer HB, Michelsen B, Provan SA, et al. Tender joint count may not reflect inflammatory activity in established rheumatoid arthritis patients - results from a longitudinal study.Arthritis Care Res (Hoboken) 2018Disclosure of Interests:None declared

Objectives To develop and test the reliability of a new semiquantitative scoring system for the assessment of cartilage changes by ultrasound in a web-based exercise as well as a patient exercise of patients with RA. Methods A taskforce of the Outcome Measures in Rheumatology Ultrasound Working Group performed a systematic literature review on the US assessment of cartilage in RA, followed by a Delphi survey on cartilage changes and a new semiquantitative US scoring system, and finally a web-based exercise as well as a patient exercise. For the web-based exercise, taskforce members scored a dataset of anonymized static images of MCP joints in RA patients and healthy controls, which also contained duplicate images. Subsequently, 12 taskforce members used the same US to score cartilage in MCP and proximal interphalangeal joints of six patients with RA in in a patient reliability exercise. Percentage agreement and prevalence of lesions were calculated, as intrareader reliability was assessed by weighted kappa and interreader reliability by Light’s kappa. Results The three-grade semiquantitative scoring system demonstrated excellent intrareader reliability (kappa: 0.87 and 0.83) in the web-based exercise and the patient exercise, respectively. Interreader reliability was good in the web-based exercise (kappa: 0.64) and moderate (kappa: 0.48) in the patient exercise. Conclusion Our study demonstrates that ultrasound is a reliable tool for evaluating cartilage changes in the MCP joints of patients with RA and supports further development of a new reliable semiquantitative ultrasound scoring system for evaluating cartilage involvement in RA.

Background Cut offs for low disease activity (LDA) using psoriatic arthritis (PsA) specific composite scores have recently been proposed.1–3 Whether these definitions adequately reflect the absence of inflammation is unknown. Objectives To evaluate these definitions against a low level of activity according to ultrasound examination. Methods We performed a prospective study on 83 PsA patients undergoing clinical and ultrasound examinations at two study visits scheduled 6 months apart. LDA was assessed using the Disease Activity index for Psoriatic Arthritis (DAPSA≤14), the Psoriatic ArthritiS Disease Activity Score (PASDAS ≤3.2), the Composite Psoriatic Disease Activity Index (CPDAI≤4), the Disease Activity Score 28 CRP (DAS28-CRP≤2.8) and the Minimal Disease Activity criteria (MDA). Ultrasound (US) evaluation was performed at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. Minimal ultrasound disease activity (MUDA) was defined as a Power Doppler (PD) score ≤1, respectively at joints, peritendinous tissue, tendons and entheses. Results LDA was present in 33.7%–65.0% of patients at baseline and in 44.3%–80.6% at follow-up examination, depending on the criteria used. MUDA was observed in 16.9% at baseline and in 30% at follow-up. At baseline only the DAPSA-LDA definition was useful to identify MUDA patients (78.6% of patients identified correctly), whereas at follow up >80% of MUDA patients were correctly classified as LDA according to DAPSA, PASDAS, CPDAI and DAS28-CRP. Only DAPSA (Sensitivity (S)=88.2%, Specificity (Sp)=40.5, p=0.033), PASDAS (S=88.2%, Sp=55.0%, p=0.002) and the MDA criteria (S=71.4%, Sp=67.3%, p=0.003) were able to discriminate patients with and without MUDA at follow-up. A global ultrasound inflammation subscore for joints and entheses (GUIS-j/e), containing the above mentioned US variables, was significantly higher in patients with active disease versus patients in LDA according to DAPSA (p=0.002) and PASDAS (p=0.013) at baseline and DAPSA (p=0.007), PASDAS (p=0.001), CPDAI (p=0.021) and the MDA criteria (p Conclusions Of all tested LDA definitions, DAPSA was overall the most efficacious in differentiating between high and low ultrasound scores and better identified patients with MUDA as compared to the other tested scores. References [1] Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: A proposed objective target for treatment. Annals of the Rheumatic Diseases69(1):48–53. [2] Helliwell PS, FitzGerald O, Fransen J. Composite disease activity and responder indices for psoriatic arthritis: A report from the GRAPPA 2013 meeting on development of cutoffs for both disease activity states and response. The Journal of Rheumatology2014;41(6):1212–7. [3] Schoels MM, Aletaha D, Alasti F, Smolen JS. Disease activity in Psoriatic Arthritis (PsA): Defining remission and treatment success using the DAPSA score. Ann Rheum Dis2016;75(5):811–8. Disclosure of Interest None declared

To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV. ispartof: ANNALS OF THE RHEUMATIC DISEASES vol:77 issue:5 pages:636-643 ispartof: location:England status: published

Objectives: To perform a systematic literature review on imaging techniques for diagnosis, outcome prediction and disease monitoring in large vessel vasculitis (LVV) informing the European League Against Rheumatism recommendations for imaging in LVV.\ud \ud \ud \ud Methods: Systematic literature review (until 10 March 2017) of diagnostic and prognostic studies enrolling >20 patients and investigating ultrasound, MRI, CT or positron emission tomography (PET) in patients with suspected and/or established primary LVV. Meta-analyses were conducted, whenever possible, obtaining pooled estimates for sensitivity and specificity by fitting random effects models.\ud \ud \ud \ud Results: Forty-three studies were included (39 on giant cell arteritis (GCA), 4 on Takayasu arteritis (TAK)). Ultrasound (‘halo’ sign) at temporal arteries (8 studies, 605 patients) and MRI of cranial arteries (6 studies, 509 patients) yielded pooled sensitivities of 77% (95% CI 62% to 87%) and 73% (95% CI 57% to 85%), respectively, compared with a clinical diagnosis of GCA. Corresponding specificities were 96% (95% CI 85% to 99%) and 88% (95% CI 81% to 92%). Two studies (93 patients) investigating PET for GCA diagnosis reported sensitivities of 67%–77% and specificities of 66%–100% as compared with clinical diagnosis or temporal artery biopsy. In TAK, one study each evaluated the role of magnetic resonance angiography and CT angiography for diagnostic purposes revealing both a sensitivity and specificity of 100%. Studies on outcome prediction and monitoring disease activity/damage were limited and mainly descriptive.\ud \ud \ud \ud Conclusions: Ultrasound and MRI provide a high diagnostic value for cranial GCA. More data on the role of imaging for diagnosis of extracranial large vessel GCA and TAK, as well as for outcome prediction and monitoring in LVV are warranted.

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise.Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise.Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts.Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.

ObjectiveTo investigate the possible occurrence of early thymic failure and premature senescence of naïve and memory T-cells in patients with axial spondyloarthritis (aSpA).MethodsProspective, cross-sectional study of consecutive patients with aSpA (n=51), rheumatoid arthritis (RA, n=51) and healthy controls (HCs, n=50). Demographic, clinical and laboratory parameters were collected in all patients and we isolated naïve (CD45RA+) and memory (CD45RO+) CD4+ and CD8+ T-cell subsets by MACS technology. T-cell receptor rearrangement excision circle (TREC) and telomere length were measured by real-time PCR. We used TRECs as a surrogate for thymus function and telomere length as an indicator of cellular senescence. Telomerase activity was analysed with the Telomeric Repeat Amplification Protocols.ResultsWe observed a premature decline of thymic output in patients with aSpA and patients with RA compared with HCs as indicated by a reduction of TREC levels in naive T-cells (aSpA: age adjusted regression coefficient (regcoeff) for CD4+CD45RA+ T-cells −2.566, p=0.023; RA regcoeff=−2.844, p=0.008). Telomere length of all CD4+ and CD8+ T-cell subsets was reduced in young patients with aSpA compared with HCs, whereas data for patients with RA were comparable with HCs. Telomerase activity was inversely correlated with telomere length in HCs (correlation coefficient (corcoeff)=−0.532, pcoeff=−0.056, p=0.697) and RA (corcoeff=−0.003, p=0.982).ConclusionsOur data indicate an age-inappropriate shrinkage of thymic output, an inappropriate shortening of telomeres in young patients with aSpA and an impaired telomerase enzyme in patients with aSpA and RA.

Background Joint destruction in rheumatoid arthritis (RA) is comprised of hyaline cartilage and bone damage, with the former more clearly associated with irreversible physical disability than bony damage. Objectives To test the reliability of a semiquantitative scoring system for the assessment of cartilage by musculoskeletal ultrasound (US) in a web-based exercise as well as a patient-based reliability study of patients with RA. Methods Static images of metacarpophalangeal (MCP) joints 2–5 in RA patients and healthy controls were acquired and a dataset of 123 anonymized images including 25 duplicate images was circulated among an international EULAR-OMERACT taskforce of 25 rheumatologist experts in US who independently scored the images using a semiquantitative scoring system. Subsequently 12 taskforce members participated in a patient-based reliability study. During this meeting MCP joints 2–5 of 6 patients with RA were assessed twice on the same day by all experts using US machines (GE) equipped with high-frequency transducers (18–22MHz) with presets calibrated for the appropriate assessment of cartilage. Participants assessed metacarpal cartilage both in the standardized longitudinal midline scan as well as by freehand technique utilizing multiple planes and scored by the semiquantitative scoring system. Intraobserver reliability was assessed by Cohen9s kappa and interobserver reliability by Fleiss9 kappa. Results The three-grade semiquantitative (Grade 0, normal cartilage; Grade 1, minimal change; Grade 2, severe change) scoring system demonstrated excellent (kappa: 0.87) to good (kappa: 0.73) intraobserver reliability in the web-based exercise and the patient-based reliability study respectively. Interobserver reliability was good in the web-based exercise (kappa: 0.64) and moderate (kappa: 0.49) in the patient-based reliability study. The dynamic technique performed slightly better than the longitudinal midline scan alone. Conclusions A semiquantitative scoring system demonstrated good intra- and moderate to good inter-observer reliability in a web-based exercise and patient-based reliability study. Our study demonstrates that US is a reliable tool for evaluating cartilage and supports the use of a new semiquantitative US scoring system for evaluating cartilage change in RA. Acknowledgements The patient-based reliability study was supported by a research grant from UCB. Disclosure of Interest None declared

Die Fruhdiagnostik gewinnt in der Rheumatologie zunehmend an Bedeutung. Chronisch entzundliche Erkrankungen sollten moglichst vor dem Auftreten radiologisch sichtbarer Schaden diagnostiziert werden und so ist der Einsatz funktioneller bildgebender Methoden wie des Ultraschalls oftmals unverzichtbar. Zur Qualitatssicherung und -verbesserung der von Rheumatologen durchgefuhrten Ultraschalluntersuchungen wurden von der Austrian Radiology-Rheumatology Initiative for Musculoskeletal Ultrasound (ARRIMUS) Empfehlungen fur die technische Ausstattung, Indikationen und Dokumentation der Ultraschall-Untersuchung, Zuhilfenahme des Ultraschalls bei Gelenkspunktion und -infiltration sowie ein Ausbildungscurriculum formuliert. Diese Empfehlungen wurden von der Osterreichischen Gesellschaft fur Rheumatologie und Rehabilitation (OGR) befurwortet und sollen als Grundlage zur Etablierung und Qualitatssicherung der Sonographie bei rheumatischen Erkrankungen in der klinischen Praxis dienen.

Die korrekte Diagnose der Polymyalgia rheumatica (PMR) gehort zu den schwierigsten Aufgaben des Rheumatologen in der klinischen Praxis. Einerseits konnen andere Erkrankungen eine PMR imitieren, andererseits sind bisher keine spezifischen Marker zur Diagnose der Erkrankung verfugbar. Neben den empirisch entwickelten Klassifikations- und Diagnosekriterien nach Hunder, Healey und Bird sind seit 2012 neue ACR/EULAR Klassifikationskriterien fur die PMR verfugbar. Deren wesentlichste Neuerung ist die Berucksichtigung des Rheumafaktors und der anti-cyclisch citrullinierten Peptid (CCP) Antikorper sowie des Ergebnisses der Ultraschalluntersuchung der Schultern und Huften. Zur Messung der Krankheitsaktivitat wurde der PMR Activity Score (PMR-AS) vorgeschlagen, der das C-reaktive Protein, die Schmerzbeurteilung durch den Patienten, die Krankheitsaktivitatseinschatzung durch den Arzt, die Morgensteifigkeit und die Fahigkeit der Elevation der Arme in einen Score kombiniert. Patienten-orientierte Outcome Parameter wurden fur die PMR bisher nicht entwickelt. Die Wertigkeit von bildgebenden Verfahren (z. B. Ultraschall, Magnetresonanztomografie oder 18 F-FDG-PET) zum Monitoring von PMR Patienten ist bislang nicht geklart.

Objective To investigate the association between psoriatic arthritis (PsA)-specific clinical composite scores and ultrasound-verified pathology as well as comparison of clinical and ultrasound definitions of remission. Methods We performed a prospective study on 70 consecutive PsA patients. Clinical assessments included components of Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Composite Psoriatic Disease Activity Index (CPDAI). Minimal disease activity (MDA) and the following remission criteria were applied: CPDAI joint, entheses and dactylitis domains (CPDAI-JED)=0, DAPSA≤3.3, Boolean9s remission definition and physician-judged remission (rem-phys). B-mode and power Doppler (PD-) ultrasound findings were semiquantitatively scored at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. Ultrasound remission and minimal ultrasound disease activity (MUDA) were defined as PD-score=0 and PD-score ≤1, respectively, at joints, peritendinous tissue, tendons and entheses. Results DAPSA but not CPDAI correlated with B-mode and PD-synovitis. Ultrasound signs of enthesitis, dactylitis, tenosynovitis and perisynovitis were not linked with clinical composites. Clinical remission or MDA was observed in 15.7% to 47.1% of PsA patients. Ultrasound remission and MUDA were present in 4.3% and 20.0% of patients, respectively. Joint and tendon-related PD-scores were higher in patients with active versus inactive disease according to CPDAI-JED, DAPSA, Boolean9s and rem-phys, whereas no difference was observed regarding enthesitis and perisynovitis. DAPSA≤3.3 (OR 3.9, p=0.049) and Boolean9s definition (OR 4.6, p=0.03) were more useful to predict MUDA than other remission criteria. Conclusions PsA-specific composite scores partially reflect ultrasound findings. DAPSA and Boolean9s remission definitions better identify MUDA patients than other clinical criteria.

Regulatory T cells (Tregs) play a dominant role in the regulation of immune responses. Quantitative and/or qualitative abnormalities of Tregs were observed in patients with autoimmune diseases and therapeutic interventions focusing Tregs are an attractive new target with the potential to cure these disorders. Biological agents approved for treatment of inflammatory rheumatic diseases transiently influence Treg prevalences and function and experimental therapies including novel biological agents, gene therapy, activation and ex vivo expansion of purified Tregs as well as substances influencing tolerogenic dendritic cells will be developed for selective Treg therapy. Although many of these interventions are effective in vitro, in animal models as well as in early clinical trials, significant concerns exist regarding the stability of Treg modifications as well as the long-term safety of Treg-based therapies.

Objective Premature senescence of lymphocytes is a hallmark of inflammatory rheumatic diseases such as rheumatoid arthritis (RA). Early T-cell aging affects conventional T-cells but is presumably not limited to this cell population; rather it might also occur in the regulatory T-cells (Tregs) compartment. In RA, Tregs fail to halt aberrant immune reactions and disease progression. Whether this is associated with early Treg senescence leading to phenotypic and functional changes of this subset is elusive so far. Methods Eighty-four RA patients and 75 healthy controls were prospectively enrolled into the study. Flow cytometry, magnetic-associated cell sorting, and cell culture experiments were performed for phenotypic and functional analyses of Treg subsets. T-cell receptor excision circle (TREC) levels and telomere lengths were determined using RT-PCR. Results In this paper, we describe the novel CD4+FoxP3+CD28− T-cell subset (CD28− Treg-like cells) in RA patients revealing features of both Tregs and senescent T-cells: Treg surface/intracellular markers such as CD25, CTLA-4, and PD-1 as well as FOXP3 were all expressed by CD28− Treg-like cells, and they yielded signs of premature senescence including reduced TREC levels and an accumulation of γH2AX. CD28− Treg-like could be generated in vitro by stimulation of (CD28+) Tregs with TNF-α. CD28− Treg-like cells insufficiently suppressed the proliferation of effector T-cells and yielded a pro-inflammatory cytokine profile. Conclusion In conclusion, we describe a novel T-cell subset with features of Tregs and senescent non-Tregs. These cells may be linked to an aberrant balance between regulatory and effector functions in RA.

Objective To compare ultrasound-verified joint inflammation between elderly-onset rheumatoid arthritis (EORA) and younger-onset rheumatoid arthritis (YORA) patients. Methods We conducted a retrospective analysis of 145 consecutive rheumatoid arthritis patients routinely assessed by sonography of wrists, metacarpophalangeal joints, and proximal interphalangeal joints, including semiquantitative scoring of synovial hypertrophy/effusion (SH/E) and power Doppler (PD) signals. Global ultrasound (GU) scores were calculated adding SH/E and PD results. EORA was defined by disease onset at age ≥60 years. Number of tender joints and swollen joints, global assessment of disease activity by physician or patient, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI) scores were recorded. Respective values for disease activity were accounted for in group comparisons using SPSS statistical software (version 18.0). Results Seventy patients were diagnosed with EORA (mean ± SD age 71.0 ± 7.3 years, 81.4% women) and 75 patients with YORA (mean ± SD age 46.8 ± 10.2 years, 86.7% women). EORA patients had higher GU scores (median 18.5 [interquartile range (IQR) 17.0] versus 12.0 [IQR 15.0], P = 0.009) and SH/E scores (median 12.0 [IQR 10.0] versus median 9.0 [IQR 9.0], P = 0.004) than patients with YORA. Patients with EORA were more likely to show PD signals in at least 1 joint than YORA patients (85% versus 72%; odds ratio 3.9 [95% confidence interval 1.3–11.5], P = 0.015). DAS28, CDAI, and SDAI scores did not differ between the groups. The sonographic pattern of joint involvement was similar in both groups, with active inflammation most commonly presenting at the wrists. Conclusion Ultrasound examination indicated higher inflammatory burden in EORA patients than in YORA patients despite similar clinical disease activity.

Objective.To prospectively evaluate the disease course and the performance of clinical, patient-reported outcome (PRO) and musculoskeletal ultrasound measures in patients with polymyalgia rheumatica (PMR).Methods.The study population included 85 patients with new-onset PMR who were initially treated with prednisone equivalent dose of 15 mg daily tapered gradually, and followed for 26 weeks. Data collection included physical examination findings, laboratory measures of acute-phase reactants, and PRO measures. Ultrasound evaluation was performed at baseline and Week 26 to assess for features previously reported to be associated with PMR. Response to corticosteroid treatment was defined as 70% improvement in PMR on visual analog scale (VAS).Results.At baseline, 77% had hip pain in addition to shoulder pain and 100% had abnormal C-reactive protein or erythrocyte sedimentation rate. On ultrasound, 84% had shoulder findings and 32% had both shoulder and hip findings. Response to corticosteroid treatment occurred in 73% of patients by Week 4 and was highly correlated with percentage improvement in other VAS measures. Presence of ultrasound findings at baseline predicted response to corticosteroids at 4 weeks. Factor analysis revealed 6 domains that sufficiently represented all the outcome measures: PMR-related pain and physical function, an elevated inflammatory marker, hip pain, global pain, mental function, and morning stiffness.Conclusion.PRO measures and inflammatory markers performed well in assessing disease activity in patients with PMR. A minimum set of outcome measures consisting of PRO measures of pain and function and an inflammatory marker should be used in practice and in clinical trials in PMR.

Klinik und Labor reichen oft nicht aus, um therapeutische Entscheidungen zu treffen. Neben Klinik und Labor bietet eine diagnosespezifische und organbezogene Bildgebung fur den Rheumatologen wichtige Zusatzinformationen zu Erst-/Differenzialdiagnose, Verlaufsbeurteilung und Prognose. Insbesondere die Fruhdiagnostik mittels funktioneller Bildgebungsmethoden wie Ultraschall und Magnetresonanztomographie gewinnt zunehmend an Bedeutung. Die Bildgebung wird bereits in einigen rheumatologischen Klassifikationskriterien berucksichtigt. Magnetresonanztomographie und Ultraschall sind zudem in die neuen Klassifikationskriterien zur axialen Spondyloarthritis bzw. Polymyalgia rheumatica integriert. Fur differenzialdiagnostische Uberlegungen sind spezifische Befunde besonders hilfreich. Zur Verlaufsbeurteilung interessieren sowohl Krankheitsstatus als auch Progression der strukturellen Schadigungen. Bei ausgewahlten Erkrankungen ermoglicht die Bildgebung sowohl bzgl. der Krankheitsprogression als auch dem Ansprechen auf die medikamentose Therapie prognostische Aussagen. Es besteht meist sehr differente Evidenz fur den Einsatz der bildgebenden Verfahren bei rheumatologischen Fragestellungen. Rheumatologische Fragestellungen sind hochst unterschiedlich und erfordern deshalb einen differenzierten Einsatz der bildgebenden Verfahren.

Immunologic memory is a critical feature of the adaptive immune system to fight recurrent infections. However, the mechanisms that shape the composition and function of the human memory T-cell pool remain incompletely understood. We here demonstrate that post-thymic human T-cell differentiation was associated with the downregulation, but not loss, of the inhibitory molecule CD5. The sensitivity of human CD8+ and CD4+ memory T cells to interleukin (IL)–15 was inversely associated with the level of CD5 expression. CD5 expression was downregulated by IL-15–mediated signaling in vitro and CD5lo memory T cells accumulated in the bone marrow. Persistent antigenic stimulation, as in the case of cytomegalovirus infection and rheumatoid arthritis (RA), was also associated with an increased number of CD5lo memory T cells. In conclusion, CD5 may be a useful marker to identify memory T-cell subsets with distinct responsiveness to the homeostatic cytokine IL-15.

Both polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) present with a broad spectrum of clinical manifestations and almost exclusively occur in the population aged over 50 years. After rheumatoid arthritis, PMR is the second most common autoimmune rheumatic disorder. Visual loss is the most feared complication in temporal arteritis, and extracranial arteries and/or aorta are more often involved in GCA than previously estimated. No specific laboratory parameter exists for diagnosis of PMR. Imaging techniques such as ultrasonography, MRI or 18F-fluorodeoxyglucose PET may be helpful in the diagnosis and evaluation of the extent of vascular involvement in these diseases. This article highlights upcoming new classification criteria for PMR, recent advances of diagnostic and therapeutic procedures as well as ongoing research on biomarkers and corticosteroid-sparing medications, which should improve management of PMR and GCA.